Cyclic nucleotides profoundly influence the normal function of the central nervous system, and there is evidence that these compounds may be involved in certain forms of mental illness as well. The data showing that known, clinically effective antipsychotic drugs can alter the intracellular concentration of cyclic nucleotides suggested the possibility that these agents may produce their antipsychotic action by modifying the concentration of cyclic AMP or cyclic GMP. We have been studying the mechanism by which antipsychotic drugs alter cyclic nucleotide levels. Antipsychotics have complex actions on the cyclic nucleotide system, for they inhibit the enzymes responsible for the biosynthesis (adenylate cyclase) and the hydrolysis (phosphodiesterase) of cyclic 3',5'-AMP. Our studies on the multiple forms of phosphodiesterase suggest an explantation for these results and provide a unifying hypothesis for explaining many of the divergent actions of antipsychotic drugs. These results showed that the brain has a high concentration of calcium-dependent modulator which can selectively increase the activity of one form of phosphodiesterase. Antipsychotics specifically inhibit this form of phosphodiesterase by selectively binding to the modular protein. Since this same protein also activates adenylate cyclase, our data suggest a common mechanism whereby antipsychotics produce their biochemical actions. By determining the specific mechanism whereby antipsychotics exert their effects on the cyclic nucleotide systems we hope to gain a better insight into the processes involved in mental illness as well as suggesting new forms of pharmacological treatment for these diseases.